The overall objectives of this project are (a) to identify and characterize the critical events of osseous repair in animal models following fracture and (b) to assess the effect on the biological repair process of different fracture stabilization modes and/or altered bone metabolism. The goals for the proposed three year period fall into two areas: 1. Completion of characterization of the biochemical events that demarcate the stages of fracture healing and the correlation of these events with morphological, radiographic and biomechanical changes during healing as affected by degree and mode of fixation. Chemical parameters to be measured are the composition and concentration of proteoglycan, collagen, mineral and lipid. Techniques include molecular sieve chromatography, SDS slab electrophoresis, indirect immunofluorescence, crystal analysis and biomechanical torque testing. 2. Determination of the biochemical and biomechanical effects of altered nutritional and metabolic status (local and distant) on fracture repair in experimental animals. Examples of such alterations are: nutritional osteomalacia, inhibition of prostaglandin synthesis and systemic fluoride administration. Current orthopaedic approaches to osseous injury, which have been derived from clinical experience and histological characterization of skeletal injury, do not consistently result in adequate fracture healing. The utilization of recently developed methodology for studying the biochemistry, histochemistry and biomechanics of skeletal tissues should permit the characterization of the critical molecular events necessary for successful fracture union both in normal and altered osseous metabolism. These results will be helpful in developing nutritional and therapeutic strategy to improve the success rate of clinical fracture healing.